(1) Field of the Invention
This invention relates to the production of human immune interferon. More particularly, the invention relates to a process for the production of human immune interferon from human peripheral blood leukocytes modulated with Mezerein or 12, 13 phorbol dibutyrate and induced by an antibiotic, the calcium ionophore A-23187.
(2) The Prior Art
Interferon was discovered by Isaacs and Lindenmann in 1957, who observed that fluids from virus-infected cell cultures contained a protein which could react with normal cells to render them resistant to infection by a wide variety of viruses. Since then, considerable work on producing leukocyte interferon has been done by Dr. Kari Cantell in Finland, see "Production and Preparation of Human Leukocyte Interferon", K. E. Mogensen and K. Cantell, Pharmac Ther. C. Vol. 1, pp. 369-381, 1977. In addition to potent antiviral effects, interferon possesses anticellular, immunoregulatory, and antitumor activities. Consequently, the use of human interferon in the treatment of cancer and viral infections in man has raised considerable interest.
Interferons are classified into three major species designated IFN-.alpha. (leukocyte), IFN-.beta. (fibroblast) IFN-.gamma. (immune). Leukocyte and fibroblast interferons are induced by viruses or synthetic polynucleotides. Immune type interferons are usually induced in primed lymphocytes by a specific antigen or in unprimed lymphocytes by T-cell mitogens.
The present invention teaches a process for producing human immune interferon (IFN-.gamma.) which is efficient and functional. A variety of procedures have been described for producing immune interferon from peripheral blood leukocytes. Some of the most popular systems employ the use of Concanavalin A, Phytohemagglutinin A, and Staphylococcal Aureus enterotoxin A. More relevant to this invention is an article, "Human Immune Interferon: Induction in Lymphoid Cells by a Calcium Ionophore," by F. Dianzani et al, in Infection and Immunity, vol. 29, pp. 561-563, August 1980, which describes the use of the calcium ionophere A-23187 as an IFN-.gamma. inducer.